Research Summary

What is the relationship between brain activity and conscious thought? One of the most important unsolved questions in science, the basis of consciousness is worthy of empiric study. Our laboratory investigates brain activity when consciousness is transiently impaired during epileptic seizures. By understanding impaired consciousness, we hope to restore normal consciousness to patients with epilepsy and other brain disorders.

Our work combines neuroimaging, electrophysiology and behavioral testing. We investigate cerebral cortical networks interacting with deeper brain structures such as the thalamus and brainstem. Current projects include single cell and larger-scale electrical recordings, neuroimaging with functional magnetic resonance imaging (fMRI) and other methods in animal models and human patients to understand changes in behavior during seizures.

Absence Epilepsy, EEG-fMRI and AttentionAbsence seizures are brief episodes of staring and unresponsiveness. Seen most commonly in children, they can disrupt school and attention performance. The mechanisms for impaired attention in absence epilepsy are not known. To determine how brain networks are affected by absence seizures we perform simultaneous fMRI and EEG recordings in children during absence seizures. We also test attention both during seizures and under normal conditions. Our work has revealed abnormal activity in specific brain regions which may serve as new targets for treatment.

Neuronal Activity and Neuroimaging in Generalized SeizuresAre “generalized” seizures truly generalized? Our work using high field (9.4-11.7T)fMRI and electrophysiology recordings from animal models suggests that s ocalled generalized absence and tonic-clonic seizures are in fact localized to specific bilateral cortical-subcortical networks. These findings may help develop targeted therapies with better efficacy and fewer side effects. In addition our direct recordings of neuronal electrical activity improve the interpretation of indirect neuroimaging measurements of brain function.

Impaired Consciousness inTemporal Lobe EpilepsyTemporal lobe seizures are the most common form of localized epilepsy. How do focal seizures impair consciousness? We propose a “network inhibition hypothesis” in which temporal lobe seizures inhibit subcortical arousal systems, causing depressed cortical function. In support of this hypothesis, we found sleep-like changes in the cortex with intracranial EEG and SPECT during temporal lobe seizures. We are now using high field (9.4 T, 11.7 T) fMRI,single neuron recordings, neurotransmitter studies, and optogenetic techniques in animal models to reveal the fundamental mechanisms of these changes, and to test novel treatment approaches.

Virtual Reality Driving Safety and other BedsideTesting in EpilepsyOne of the most devastating effects of altered consciousness in epilepsy is impaired driving safety. To determine how epileptic seizures affect performance, we use virtual-reality driving simulation during video/EEG monitoring while patients are in the hospital. In addition, we have developed a prospective bedside testing battery, the Responsiveness in Epilepsy Scale (RES). These testing methods provide better information to patients and physicians making decisions about driving, and may help identify brain areas crucial for impaired consciousness in epilepsy.

Technical Advances in Epilepsy Surgery LocalizationSome patients have seizures that are so severe that they cannot be controlled by medicine. Many of these patients can be cured if we can identify a specific damaged region of the brain that can safely be removed and prevent the triggering of their seizures. We have recently developed novel approaches to target surgery to the correct location in the brain, including:(i) 3D color movies of the “brainwave” electroencephalogram (EEG) in patients with epilepsy show where the seizures start, making safe and effective surgery much more feasible; (ii) innovative methods using single photon emission computed tomography (SPECT) and positron emission tomography (PET) tracers can pinpoint the region of seizure onset for surgical planning.

Preventing EpilepsyOne crucial goal is the prevention of epilepsy before it even begins. We found in a genetic form of epilepsy that if we treat rat pups with anti-seizure medication from a very early age (even before seizures started) we greatly reduce their tendency to have seizures as adults. In addition, we found in a recent review of human studies of the same form of epilepsy that early and effective treatment may improve long-term outcome. This is a paradigm shift from current treatment strategies which view seizure medications as suppressing the symptoms, not the underlying disease.

The findings also raise the hope that as genes are identified and enable epilepsy to be predicted, beneficial treatments may be started even before symptoms begin.

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